Latest on VTE in Pediatric IBD

MA Aardoom et al. JCC 2021; https://doi.org/10.1093/ecco-jcc/jjab171 The incidence and characteristics of venous thromboembolisms in paediatric-onset inflammatory bowel disease; a prospective international cohort study based on the PIBD-SETQuality Safety Registry

Design: 2016-2020: paediatric gastroenterologists prospectively replied to the international Safety Registry, monthly indicating whether they had observed a VTE case in a patient <19 years with IBD. n=24,802 PIBD patients

Key findings:

  • Twenty cases of VTE were identified (30% Crohn’s disease)
  • The VTE incidence was 3.72 [95%CI 2.27 – 5.74] per 10,000 person-years, 14-fold higher than in the general pediatric population (0.27 [95%CI 0.18-0.38], p<0.001)
  • All but one patient had active IBD, 45% were using steroids and 45% hospitalized.
  • Cerebral sinus venous thrombosis was most frequently reported (50%) VTE

My take: The absolute risk of VTE is low in the pediatric population. In those with active disease, the presence of CVC and use of steroids are known risk factors and require consideration of, at minimum, nonpharmacologic interventions.

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Stratifying Risk of Clots in Inflammatory Bowel Disease

T Naito et al. Gastroenterol 2021; 160: 771-780. Full text: Prevalence and Effect of Genetic Risk of Thromboembolic Disease in Inflammatory Bowel Disease

Background: 10% of healthy subjects are genetically at high risk for thromboembolic disease (TED). For adults with inflammatory bowel disease, TED is “largest cause of mortality in
patients”

Key findings:

  • In total, this retrospective study had 792 IBD patients who had both whole-exome sequencing and genotyping data to identify thrombophilia pathogenic variants. 122 of 792 IBD patients (15.4%) as genetically high risk for TED.
  • Genetic TED risk was significantly associated with increased TED event (odds ratio,2.5; P ¼ .0036).
  • Patients with high TED genetic risk more frequently had thrombosis at multiple sites (78% vs 42%, odds ratio, 3.96; P ¼ .048)

“Our analyses demonstrate that approximately 1 in 7 patients with IBD have odds 2.5 times higher than nongenetically high-risk patients with IBD for experiencing TED.” The risk of TED in IBD is generally 3- to 4-fold higher than the general population

My take: In children, the risk of clots is much lower than in adults. Thus, the potential to identify those at highest risk would be useful in order to target interventions. Also, patients at higher risk for TED may affect choice of treatment (eg. avoiding JAK inhibitors).

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From The Onion:

From The Onion

Catheter-Related Venous Thrombosis in Pediatric Patients with Inflammatory Bowel Disease

A recent retrospective study (CE Diamond et al. J Pediatr 2018; 198: 53-9) examined the issue of catheter-related venous thrombosis in pediatric inflammatory bowel disease (IBD) patients (2015-17).

In total, 40 patients (47 hospitalizations, median age 14 yrs) with IBD were reviewed.  At the discretion of the treating physician, anticoagulation therapy (AT) with enoxaparin was administered in some children due to the recognized increase risk of venous thromboembolism (VTE).  This protocol did NOT evaluate for subclinical venous thrombotic events.  Detection of VTE was undertaken in those who became symptomatic (eg. pain or swelling).

AT protocol: 

  • In patients less than 40 kg, the starting dose of enoxaparin was 0.5 mg/kg/dose SC every 12 hrs with anti-factor Xa levels drawn 4-6 hours after the patient had received at least 2 doses with a target level of 0.1-0.3 U/mL. The first dose was administered on the same day as CVC placement but after placement.
  • In patients >40 kg, a fixed dose of 40 mg of enoxaparin SC every 24 hrs without laboratory monitoring

Key findings:

  • 5 of 23 (22%) hospitalizations without AT developed VTE; in contrast 0 of 24 with AT prophylaxis.  Mean duration of AT was 11 days.
  • All five who developed VTE had complete resolution after treatment with anticoagulation Rx. No cases of genetic thrombophilia were identified.
  • Bleeding issues were similar in the two groups –46% of those receiving AT Rx required at least one blood transfusion compared with 39% who did not receive AT Rx.

Overall, these groups (with and without AT Rx) had similar demographic features and had severe active IBD.  Most were receiving biologic therapy and the majority were receiving steroids.  The authors observed a trend towards more use of AT over the study period, “suggesting increased comfort levels of treating physician…even in the presence of rectal bleeding.”

My take: This relatively small study found that AT Rx reduced the rate of CVC-related venous thrombosis.  A larger prospective study is needed to confirm the potential benefit of AT treatment.

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Artwork near Azalea Drive/Chattahoochee river

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications (along with potential adverse effects) should be confirmed by prescribing physician.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Venous Thromboembolism: A Good Question for Pediatric Collaboration

Two recent clinical review articles (see below) indicate that most adults with inflammatory bowel disease (IBD) admitted to the hospital would benefit from venous thromboembolism (VTE) prophylaxis.  Since children with IBD have a lower risk of VTE, it is unclear whether more efforts at VTE prophylaxis are needed in the pediatric population.  Previous studies have shown that in those IBD patients less than 20 years, the incidence rate was 8.9 per 10,000 person years.  In contrast, in those IBD patients older than 60, the incidence rate was 54.6 per 10,000 person years (VTE with IBD | gutsandgrowth).

  • Inflammatory Bowel Dis 2015; 21: 1195-1203.
  • Inflammatory Bowel Dis 2015; 21: 1204-1213.

In the first article, the authors review common risk factors and disease-specific risk factors.  They state the following:

Because hospitalization puts the patient at greater risk for TE compared with an outpatient setting, all hospitalized patients should receive anticoagulant therapy in the absence of severe bleeding, even if the patients are in remission.

The second review describes epidemiological data, pathophysiology, and VTE prevention. They also state the following:

Currently, the most effective strategy for preventing VTE in hospitalized patients with IBD with active disease is prophylactic anticoagulation.  In fact, all of the current guidelines for the management of patients with IBD suggest the use of anticoagulants to prevent VTE.

The authors note that the rates of thromboprophylaxis are “still unacceptably low.”

Bottomline: In adults with active IBD, VTE prophylaxis is recommended. In the pediatric population due to the lower incidence of VTE, more study is needed –perhaps another project for ImproveCareNow.

Briefly noted:

Cochrane Review of Vedolizumab for Ulcerative Colitis.  Inflammatory Bowel Dis 2015; 21: 1151-59.  Based on four studies (n=606 patients) with low risk of bias, pooled analysis showed that vedolizumab was superior to placebo for induction of remission (RR=0.86), clinical response (RR=0.82), endoscopic remission (RR=0.82) and for achieving remission at 52 weeks in week 6 responders (RR=2.73).  No statistically significant difference was observed in the incidence of adverse events between vedolizumab and placebo.

Zoo Atlanta

Zoo Atlanta

VTE with IBD

In our children’s hospital, work is underway to systematically screen children for risk factors for venous thromboembolism (VTE) and to establish an algorithm to lower the risk of a VTE with either mechanical or pharmacologic treatments. One of the risk factors has been the presence of inflammatory bowel disease (IBD).  The absolute risk of IBD for VTE is not clear.  However, a recent study relates the risk among a large Danish population of adults and children (Gut 2011; 60: 937-43).

The study included 49,799 patients with IBD (14,211 Crohn’s, 35,229 UC) and compared with 477,504 members of the general population.  VTE risk for IBD was increased with HR of 2.0.  The incidence of VTE increased with age; however, the RR was higher in younger patients.  Among those less than 20 years, HR was 6.6 for VTE; HR 6.0 for DVT and 6.4 for PE.  In this age group, “unprovoked” VTE had HR of 4.5.  Unprovoked VTE was defined as event occurring without malignancy, recent surgery, pregnancy or fracture.

Although the relative risk is increased, the authors caution that the absolute risk in younger patients is low.  In those IBD patients less than 20 years, the incidence rate was 8.9 per 10,000 person years.  In contrast, in those IBD patients older than 60, the incidence rate was 54.6 per 10,000 person years.  There did not seem to be a significant difference between Crohn’s disease and ulcerative colitis in absolute or relative risk. The authors conclude that in those IBD patients younger than 20 years without ‘other VTE risk factors or limited mobility, the benefits of prophylaxis may no longer outweigh the risks.”  In older patients (>60 years), even outpatients experiencing flares might benefit from VTE prophylaxis.

Additional references:

  • -NEJM 2012; 366: 860 (letter to editor). Authors emphasize importance of VTE with UC, especially during flares.
  • -Lancet 2010; 375: 657-63. VTE with active IBD and in remission.
  • -Clin Gastroenterol Hepatol 2008; 6: 41-5. Thrombosis with IBD.
  • -Gut 2004; 53: 542-8. IBD -risk factor for VTE?
  • -Gut 2004; 53 (suppl 5): v1-16. IBD guidelines for management.